摘要
目的:构建阿苯达唑自微乳给药系统(albendazole-loaded self microemulsion drug delivery system,ABZ-SMEDDS),提高难溶性药物的溶出度和口服生物利用度。方法:通过伪三相图的建立优化自乳化微乳的处方组成,测定其粒径、载药量、包封率以及微观形态,并考察其体外释药效果和在结肠腺癌Caco-2细胞模型上的细胞毒性及细胞摄取情况,最后对ABZ-SMEDDS的大鼠口服生物利用度进行研究。结果:ABZ-SMEDDS最优处方组成为丁香油、聚氧乙烯氢化蓖麻油RH40和聚乙二醇400,其质量比为0.20∶0.64∶0.16。最优处方制备的ABZ-SMEDDS粒径为(52.14±1.82)nm,多分散指数为0.084±0.006,载药量为(36.60±1.20)mg/g,包封率为(98.12±2.20)%,透射电镜显示微乳呈圆球状。体外释放与细胞实验结果显示,相比于原料药,ABZ-SMEDDS在不同溶出介质中均能显著提高药物溶出度并促进药物的跨膜吸收。体内药动学结果显示,与原料药相比,ABZ-SMEDDS的相对生物利用度提高至151.95%。结论:制备的ABZ-SMEDDS能够较好地提高难溶性药物的溶出度和口服生物利用度。
Objective:To establish an albendazole-loaded self-microemulsifying drug delivery system(ABZ-SMEDDS)to improve the solubility and oral bioavailability of the water poorly soluble drug.Methods:The composition of the self-microemulsion prescription was optimized by the establishment of pseudo-triphasic diagrams,then the particle size,drug loading,encapsulation rate,and micromorphology were determined.The in vitro drug release and cytotoxicity and cellular uptake were investigated on a Caco-2 cell model,and finally,the oral bioavailability of ABZ-SMEDDS in rats was investigated.Results:The optimal prescription composition of ABZ-SMEDDS is clove oil,polyoxyethylene hydrogenated castor oil RH40 and polyethylene glycol 400 in a mass ratio of 0.20∶0.64∶0.16.The particle size of ABZ-SMEDDS was(52.14±1.82)nm with a polydispersity index of 0.084±0.006.The drug loading and encapsulation efficiency were(36.60±1.20)mg/g and(98.12±2.2)%,respectively.The results of in vitro release and cell experiments showed that the dissolution rate of ABZ-SMEDDS in different dissolution media were greatly improved compared with ABZ,and it can promote the transmembrane absorption of drugs.Pharmacokinetic results in vivo showed that the relative oral bioavailability of ABZ-SMEDDS in rats was increased to 151.95%compared with the free drug.Conclusion:SMEDDS could be a potential carrier for the enhancement of drug dissolution and oral bioavailability of poorly water soluble drugs.
作者
盛新春
王海桥
朱源
刘宏飞
SHENG Xinchun;WANG Haiqiao;ZHU Yuan;LIU Hongfei(School of Pharmacy,Jiangsu University,Zhenjiang Jiangsu 212013;Jiangsu Wan′gao Pharmaceutical Co.,Ltd,Nantong Jiangsu 226100;Jiangsu Su′nan Pharmaceutical Industrial Co.,Ltd,Zhenjiang Jiangsu 212400,China)
出处
《江苏大学学报（医学版）》
CAS
2024年第6期542-549,共8页
Journal of Jiangsu University：Medicine Edition
基金
镇江“金山英才”高层次领军人才培养计划(第六期“169工程”)培养对象科研项目
句容市社会发展科技计划项目(ZA42109)。
关键词
阿苯达唑
自乳化微乳
体外溶出
细胞摄取
口服生物利用度
albendazole
self-microemulsion
dissolution in vitro
cellular uptake
oral bioavailability
